What causes Opioid Withdrawal Symptoms? 

#POCM #MedEd

With chronic use, opioids constantly stimulate mu-receptors. Think of this as putting a continuous BRAKE on the cell's "go" signal. This occurs primarily through G-protein-coupled inhibition of adenylyl cyclase. This suppresses neuronal activity, especially in the locus coeruleus which is the brain's primary norepinephrine factory.

To maintain homeostasis, the body/brain compensates by upregulating excitatory systems. The brain starts pushing harder on the accelerator (norepinephrine production) to counteract the constant opioid brake. A new, fragile balance is set.

When opioids are stopped, the brake is abruptly released. But the accelerator is still floored. The result is a massive, unopposed surge of norepinephrine from a now hyper-excitable locus coeruleus.

This norepinephrine surge is directly responsible for the classic signs of withdrawal:

- Tachycardia & Hypertension
- Anxiety, Agitation, & Irritability
- Diaphoresis & Piloerection (goosebumps)
- Mydriasis (dilated pupils)
- GI Upset (cramping, diarrhea)

This pathophysiology makes treatment more intuitive. 

We have two main strategies:

- Opioid Agonists (MOUD like Methadone, Buprenorphine): Re-apply the brake.

- Alpha-2 Agonists (Clonidine, Lofexidine): Directly dampen the accelerator by inhibiting norepinephrine release.

Opioid withdrawal is a predictable state of noradrenergic hyperactivity. It's caused by the sudden removal of opioid-induced inhibition on a nervous system that has already upregulated its excitatory tone. Remembering the "brake and accelerator" model clarifies both the symptoms and our treatment rationale.


Check out our most recent #POCM publications on Opioid Withdrawal!

Opioid Withdrawal and OUD: Clinical Review Article

http://www.pointofcaremedicine.com/review-article/oud-and-opioid-withdrawal

Opioid Withdrawal: Inpatient Admission

http://www.pointofcaremedicine.com/inpatient-admission/oud-and-opioid-withdrawal

13 Essential Facts for Managing Opioid Withdrawal in 2025 

http://www.pointofcaremedicine.com/blog-post/13-essential-facts-for-managing-opioid-withdrawal-in-2025

Understanding Opioid Withdrawal

A patient is admitted with a severe infection but is also in opioid withdrawal. 

They're agitated, diaphoretic, and asking to leave.

This is a medical emergency and how you manage withdrawal can determine whether patients stay for life-saving care.

Managing opioid withdrawal in the hospital,

- Thread - 

#POCM #MedEd

To learn more and reference this material in the future, check out our recent POCM Opioid Withdrawal publications!

Opioid Withdrawal and OUD: Clinical Review Article

http://www.pointofcaremedicine.com/review-article/oud-and-opioid-withdrawal

Opioid Withdrawal: Inpatient Admission

http://www.pointofcaremedicine.com/inpatient-admission/oud-and-opioid-withdrawal

13 Essential Facts for Managing Opioid Withdrawal in 2025 

http://www.pointofcaremedicine.com/blog-post/13-essential-facts-for-managing-opioid-withdrawal-in-2025

First, rule out other emergencies.

Opioid withdrawal symptoms (tachycardia, fever, anxiety) can mimic other diseases. 

Before you anchor on withdrawal, consider this differential:

- Sepsis (possibly from endocarditis or epidural abscess)
- Concurrent alcohol or benzodiazepine withdrawal
- Influenza or severe gastroenteritis

Triage the patient with COWS

The Clinical Opiate Withdrawal Scale (COWS) is an objective guide. It quantifies severity and dictates treatment, especially when starting buprenorphine.

- COWS 5-12: Mild
- COWS 13-24: Moderate
- COWS 25-36: Moderately Severe
- COWS >36: Severe

Your initial orders set the stage.

- Labs: UDS (note: fentanyl may need a specific assay), CBC, CMP, HIV/HCV Abs. Consider blood cultures if an infection is suspected.

- EKG: Get a baseline QTc, especially if you're considering methadone.

- Pain Management: Multimodal pain management including additional opioid agonists, often at high doses

MOUD is the Standard of Care

Symptom management alone is insufficient. The standard of care is initiating Medications for Opioid Use Disorder (MOUD). It should be offered to every patient.

The two first-line inpatient options are buprenorphine and methadone.

- Buprenorphine: Partial agonist. MUST be in moderate withdrawal (COWS generally >12) to avoid precipitated withdrawal. Tricky with fentanyl's long half-life.

- Methadone: Full agonist. Can be started immediately. No need to wait for withdrawal. Requires QTc monitoring.

Control Symptoms

While MOUD is ramping up, keep the patient comfortable.

- Autonomic: Clonidine
- Nausea: Ondansetron
- Diarrhea: Loperamide
- Myalgias: NSAIDs/Acetaminophen
- Anxiety/Insomnia: Hydroxyzine/Trazodone
- Dehydration: IV Fluids

The Goal is more then detox

Simply "detoxing" a patient without a bridge to outpatient care is dangerous. It transiently reduces their tolerance, placing them at increased risk of fatal overdose upon relapse.

Your goal is linkage to long-term care; work closely with your CM/SW teams!

Summary

Managing opioid withdrawal in the hospital is a high-stakes opportunity. 

Untreated withdrawal is a primary driver of patients leaving AMA with life-threatening conditions.

Treat aggressively with opioid agonists and MOUD (buprenorphine or methadone) and plan for a seamless handoff to outpatient care.


Managing Opioid Withdrawal Inpatient

Your patient with BPPV is back. Again. 

You perform a flawless Epley maneuver, and they feel better. 

But a few months later, they return with the same debilitating vertigo.

What if the root cause isn't just mechanical, but biochemical? 

And could a simple vitamin be the key?

 🧵

1. OTOLITH 101 

BPPV happens when otoconia—tiny calcium carbonate crystals—break loose and migrate into the semicircular canals.

We focus on getting them out. But we should also ask: why did they become unstable in the first place? The answer lies in their composition.

2. THE VITAMIN D CONNECTION 

Otoconia are made of calcium. Their structural integrity depends on precise calcium homeostasis.

Vitamin D is the master regulator of intestinal calcium absorption and balance.

Low Vitamin D → Impaired Calcium Metabolism → Otolith Degeneration.

The crystals become brittle and are more likely to detach.

3. THE CLINICAL PEARL 

For patients with recurrent or idiopathic BPPV, the workup shouldn't stop at the Dix-Hallpike.

Clinical studies show that correcting Vitamin D deficiency can significantly reduce BPPV recurrence rates. It’s a simple, low-risk, and potentially high-yield intervention.  

https://pubmed.ncbi.nlm.nih.gov/38384364/

4. A PROACTIVE APPROACH 

For the patient with recurrent BPPV, consider this simple addition to your plan:

Perform the canalith repositioning maneuver.

Check a 25-hydroxyvitamin D level.

Supplement if deficient.

This shifts management from purely reactive (the maneuver) to proactive (addressing the underlying instability).

SUMMARY 

When managing recurrent BPPV, think beyond the Epley. An unstable biochemical environment, often driven by low vitamin D, may be the root cause. Checking and repleting vitamin D is a simple strategy that can help break the frustrating cycle of recurrence.

BPPV and Vitamin D

A patient presents with dizziness after a night out. 🍺

We often label it "intoxication," but what’s the specific neuro-vestibular cascade? 

It's a fascinating "perfect storm" of central and peripheral dysfunction.

Let's break down the pathophysiology of "the spins."

 🧵

1. The Central Hit: Cerebellar Disruption 

First, alcohol acts as a potent CNS depressant, with a particular affinity for the cerebellum.

Suppression of the vestibulocerebellum impairs balance integration, leading to ataxia. It also disrupts brainstem neural integrators, causing the classic gaze-evoked nystagmus.

2. The Peripheral Cause: Inner Ear Chaos 

Here's the key to "the spins." Alcohol diffuses into the cupula of the semicircular canals faster than into the surrounding endolymph fluid.

This creates a density mismatch, making the cupula temporarily buoyant. It now moves with gravity, falsely signaling head rotation to the brain.

3. The Result: Positional Alcohol Nystagmus (PAN) 

This false signal of rotation results in true vertigo and nystagmus, known as Positional Alcohol Nystagmus (PAN).

This is why symptoms are notoriously worse when lying down or turning the head in bed—these positional changes maximally stimulate the now gravity-sensitive cupula.

4. The Visual-Vestibular Conflict 

To make matters worse, alcohol impairs ocular motor control.

Smooth pursuit and saccadic eye movements become imprecise. This creates a sensory mismatch between the faulty vestibular signals and the struggling visual system, amplifying the sense of disorientation and instability.

Summary 

Alcohol-induced vertigo is not a vague symptom; it’s a multi-system failure.

Central: Cerebellar/brainstem depression impairs coordination.

Peripheral: Cupula-endolymph density mismatch creates false rotation signals (PAN).

Visual: Ocular motor deficits add sensory conflict.

Understanding this pathway helps differentiate it from other vestibular pathologies.

Dizziness: Alcohol's Neuro Effects

A patient presents with spinning vertigo and nausea. You reach for meclizine.

But what are we actually treating? And more importantly, when might this reflex be the wrong move?

A short thread on the precise role of antihistamines in vertigo.

🧵

1. The Central Suppressant Effect 

Antihistamines don't fix the underlying cause of vertigo. 

They are vestibular suppressants.

By blocking H1 receptors in the brainstem (vestibular nuclei, vomiting center), they dampen the chaotic signals causing vertigo and nausea. Many also have anticholinergic effects, adding to this suppression.

2. The Right Indications: Peripheral Vertigo 

Their primary role is providing short-term symptomatic relief in acute peripheral vestibulopathies like: 
• Vestibular neuritis
• Labyrinthitis

Think of them as a tool to manage distress while the underlying condition resolves.

3. The Wrong Indications: When to Avoid 

Antihistamines are NOT first-line therapy for:
• BPPV: Symptoms are too brief for meds to be effective. The treatment is canalith repositioning (e.g., Epley maneuver).
• Central Vertigo (e.g., stroke): They are less effective and can obscure the diagnosis.

4. The Critical Pitfall: The Danger of Long-Term Use 

This is the most important pearl.

Using vestibular suppressants for more than a few days is counterproductive. It impairs central compensation—the brain's natural ability to recalibrate and recover from a vestibular injury.

Prolonged use can lead to chronic imbalance.

Summary 

Think of antihistamines as a temporary bridge, not a destination.

They offer short-term symptomatic control in specific acute peripheral syndromes. They don't cure the cause, and using them long-term actively hinders the patient's recovery.

Use wisely, then stop.

Antihistamines in Vertigo

Your patient has brief, intense vertigo with head turns. The diagnosis is likely BPPV.

One of the most satisfying procedures in medicine is the cure; and you can do it in 5 minutes at the bedside.
 
A thread on mastering the Epley maneuver.

🧵

THE PATHOPHYSIOLOGY 

BPPV is a mechanical problem.

Tiny calcium crystals (otoconia) get dislodged from the utricle and fall into a semicircular canal (usually the posterior).

When the head moves, these "ear rocks" roll around, sending a false signal of motion to the brain.

ENTER: THE EPLEY MANEUVER 

The goal isn't to dissolve the crystals. It's to guide them out.

The Epley maneuver uses a specific sequence of head movements to leverage gravity, rolling the otoconia out of the posterior canal and back into the utricle, where they no longer cause issues.

STEP 1: CONFIRM THE DIAGNOSIS 

Before you Epley, you must Dix-Hallpike.

This test not only confirms posterior canal BPPV but, crucially, tells you WHICH side is affected. The Epley must be performed starting toward the symptomatic side.

Don't skip this step.

THE MANEUVER: A 4-STEP GUIDE 

Dix-Hallpike Position: Head turned 45° to the affected side, then lie back quickly. (This provokes vertigo).

Head Rotation: Slowly turn head 90° to the unaffected side.

Body Roll: Roll onto the shoulder of the unaffected side, now looking toward the floor.

Sit Up: Slowly bring the patient to a sitting position.

Clinical Pearl: Hold each position for 30-60 seconds to allow the otoconia to settle.

WHEN EPLEY ISN'T ENOUGH 

If standard Epley fails, consider other possibilities:

• Cupulolithiasis (stuck otoconia): The rapid Semont (Liberatory) Maneuver may be needed to dislodge adherent debris.

• Horizontal Canal BPPV: If nystagmus is horizontal, the Epley won't work. Use the Lempert Maneuver (the "barbecue roll").

SUMMARY 

BPPV is a mechanical disorder requiring a mechanical fix. 

The Epley maneuver is a safe, highly effective, first-line bedside procedure for posterior canal BPPV.

Master the Dix-Hallpike to diagnose, then master the Epley to treat. It's one of the most rewarding skills in a clinician's toolkit.

Mastering The Epley Maneuver

A patient reports intense vertigo every time they roll over in bed. 

You suspect Benign Paroxysmal Positional Vertigo (BPPV), the most common cause.

But before you can treat it, you must diagnose it. Your choice between two simple bedside maneuvers is critical.

Here's how to get it right.

🧵

First, the "Why": BPPV is a mechanical problem. 

Dislodged otoconia ("ear crystals") fall into a semicircular canal. When the head moves, the crystals shift, creating a false signal of motion. 

Our goal isn't just to confirm BPPV—it's to find which canal the crystals are in.

THE DIX-HALLPIKE MANEUVER 

This is your go-to for the most common type: Posterior Canal BPPV.

• Test: Patient seated, turn head 45°, then rapidly bring them supine with head extended.
• Positive Finding: A brief latency, then upbeat-torsional nystagmus.

If you see this, you've found your culprit.

THE SUPINE ROLL TEST 

What if the Dix-Hallpike is negative, but suspicion remains high? Think Horizontal Canal BPPV.

• Test: Patient supine, head slightly elevated. Rapidly turn the head 90° to one side, then the other.
• Positive Finding: Purely horizontal nystagmus.

Interpreting the Supine Roll 

This is where a key pearl lies. The direction of the nystagmus tells you more.

• Geotropic Nystagmus (beats toward the ground): Suggests free-floating crystals (canalithiasis).
• Apogeotropic Nystagmus (beats away from the ground): Suggests crystals stuck to the cupula (cupulolithiasis).

QUICK DIAGNOSTIC CHECKLIST 

Suspect Posterior Canal? 
→ Use Dix-Hallpike
→ Look for upbeat-torsional nystagmus

Suspect Horizontal Canal? 
→ Use Supine Roll Test
→ Look for horizontal nystagmus (geotropic or apogeotropic)

The bottom line: Don't just stop at diagnosing BPPV. Use the Dix-Hallpike and Supine Roll maneuvers to pinpoint the affected canal. 

Accurate diagnosis is the first and most crucial step toward selecting the correct (and highly effective) repositioning maneuver.

Diagnosing Benign Paroxysmal Positional Vertigo

A patient's eyes are moving rapidly. Is it a saccade or nystagmus?

Getting this right is fundamental to the neuro exam. One is normal, the other can signal serious pathology.

Let's break down the difference.  

🧵

1. SACCADES: Purposeful Gaze Shifts 

Saccades are fast, voluntary eye movements that redirect your gaze. Think of scanning a room or reading a line in a book.

They are generated by the frontal eye fields & brainstem centers (PPRF, riMLF).

Key Point: They are normal and essential for vision.

2. NYSTAGMUS: An Involuntary Drift 

Nystagmus is a rhythmic, involuntary oscillation. It has two parts:

Slow Phase: A pathological drift away from the target.

Fast Phase: A corrective saccade snapping back.

We name nystagmus by its fast phase, but the slow phase reveals the true problem.

3. THE CORE DISTINCTION 

Saccade = A single, purposeful movement to acquire a new target. It's an action.

Nystagmus = A continuous, rhythmic oscillation due to a failure in gaze-holding or vestibular input. It's a system failure.

One is a feature, the other is often a bug.

4. BEDSIDE PEARL: Why It Matters 

In a patient with vertigo, this distinction is critical. 

Spontaneous nystagmus often points to a vestibular or central (e.g., cerebellar) lesion.

Pro-Tip: In peripheral vestibular nystagmus, the slow phase typically drifts toward the side of the lesion.

SUMMARY 

Saccades are how our eyes intentionally look around. 

Nystagmus is an involuntary drift that signals an imbalance in the vestibular or central nervous systems.

Mastering this difference transforms your ability to interpret the eye exam, especially in dizzy patients.

Eye Movements: Saccade vs. Nystagmus

A patient with vertigo isn't just dizzy—they're often profoundly nauseated. 

But why does a spinning room make the stomach churn?
 
The answer is a fascinating case of mistaken identity, rooted in an ancient evolutionary defense mechanism.

Let's break it down. 

🧵

1. The Sensory Mismatch 

Your brain requires consensus from three key systems to understand your position in space:

Vestibular system: Senses motion & balance.

Visual system: Sees your surroundings.

Proprioception: Senses where your body is.

Vertigo occurs when these signals don't align.

2. The Neural Alarm System 

When the vestibular system reports motion that your eyes don't see, the brain receives conflicting data.

This conflict triggers an alarm, sending signals from the vestibular nuclei directly to the brainstem's "vomiting center" (nucleus tractus solitarius & area postrema).

3. The Neurotoxin Hypothesis 

But why nausea? Evolutionarily, one of the primary causes of such sensory conflict was ingesting a neurotoxin from spoiled food or poisonous plants.

The brain interprets this mismatch as a sign of poisoning. It can't distinguish a vestibular disorder from a toxin.

4. The Protective Reflex 

Faced with potential poisoning, the brain defaults to a simple, life-saving protocol: "When in doubt, get it out."

Nausea and vomiting are not just side effects; they are a purposeful, albeit misguided, attempt to expel a perceived toxin before it can cause more harm.

The Takeaway

Nausea in vertigo is not a random symptom—it’s a hardwired, primitive defense mechanism. 

The brain interprets sensory mismatch as a threat and activates its best defense against poisoning.

A clinical pearl rooted in evolutionary biology.

Why Vertigo Causes Nausea

A patient presents with vertigo, tinnitus, and hearing loss. 

This triad screams Ménière's Disease, but what's really happening in the inner ear?

The pathophysiology is more than just a buzzword—it's key to grasping this challenging diagnosis.

🧵

THE CORE MECHANISM: Endolymphatic Hydrops
 
At its heart, Ménière’s is caused by endolymphatic hydrops: an excessive buildup of endolymph fluid in the inner ear.

Think of "hydrops" as a fluid overload in a closed system. This isn't just extra fluid; it's destructive pressure.


A TALE OF TWO FLUIDS 

The inner ear contains two fluids:
- Endolymph: Inside the membranous labyrinth (the closed system). 
- Perilymph: Surrounds the labyrinth. 

In Ménière's, endolymph volume increases, raising pressure. This pressure distorts and damages the delicate structures for balance and hearing.

POTENTIAL TRIGGERS FOR HYDROPS 

The hydrops is the result, not the root cause. The true trigger is often multifactorial and can be elusive.

Consider this differential:
• Viral infections (Herpes family)
• Autoimmune reactions
• Anatomic abnormalities
• Allergies
• Genetic predisposition
• Head trauma

CONNECTING SYMPTOMS TO PATHOPHYSIOLOGY 

The symptoms are a direct readout of the inner ear pressure.

• Vertigo: Pressure on the vestibular system.
• Hearing Loss/Tinnitus: Pressure on the cochlea.
• Aural Fullness: A direct sensation of the hydrops itself.

SUMMARY: A Cascade of Events 

Ménière's Disease is the clinical syndrome. Endolymphatic hydrops is the mechanism.

But the hydrops is a consequence of an underlying trigger—from viral to autoimmune. This complexity is why Ménière's remains a formidable diagnostic and therapeutic challenge.